The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(gamma-benzyl L-glutamate)-b-hyaluronan polymersomes
UPADHYAY, Kamal Kumar
Pharm Dept, Fac Technol & Eng, Univ Baroda
Laboratoire de Chimie des Polymères Organiques [LCPO]
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Pharm Dept, Fac Technol & Eng, Univ Baroda
Laboratoire de Chimie des Polymères Organiques [LCPO]
UPADHYAY, Kamal Kumar
Pharm Dept, Fac Technol & Eng, Univ Baroda
Laboratoire de Chimie des Polymères Organiques [LCPO]
Pharm Dept, Fac Technol & Eng, Univ Baroda
Laboratoire de Chimie des Polymères Organiques [LCPO]
SCHATZ, Christophe
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 3 LCPO : Polymer Self-Assembly & Life Sciences
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 3 LCPO : Polymer Self-Assembly & Life Sciences
LE MEINS, Jean-Francois
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 3 LCPO : Polymer Self-Assembly & Life Sciences
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 3 LCPO : Polymer Self-Assembly & Life Sciences
LECOMMANDOUX, Sebastien
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 3 LCPO : Polymer Self-Assembly & Life Sciences
< Réduire
Laboratoire de Chimie des Polymères Organiques [LCPO]
Team 3 LCPO : Polymer Self-Assembly & Life Sciences
Langue
en
Article de revue
Ce document a été publié dans
Biomaterials. 2010, vol. 31, n° 10, p. 2882-2892
Elsevier
Résumé en anglais
We have investigated the intracellular delivery of doxorubicin (DOX) loaded poly(gamma-benzyl L-glutamate)block-hyaluronan (PBLG-b-HYA) based polymersomes (PolyDOX) in high (MCF-7) and low (U87) CD44 expressing cancer cell ...Lire la suite >
We have investigated the intracellular delivery of doxorubicin (DOX) loaded poly(gamma-benzyl L-glutamate)block-hyaluronan (PBLG-b-HYA) based polymersomes (PolyDOX) in high (MCF-7) and low (U87) CD44 expressing cancer cell models. DOX was successfully loaded into polymersomes using nanoprecipitation method and in vitro drug release pattern were achieved at pH 5.5 and 7.4 up to 10 days. Block copolymer vesicles without loaded DOX were non cytotoxic in both cells at concentration 150-650 mu g/mL. Flow cytometry data suggested successful uptake of PolyDOX in cells and high accumulation was found in MCF-7 than U87 cells. Microscopy imagings revealed that in MCF-7 cells PolyDOX was more in cytoplasm and free DOX in nuclei, whereas in U87 cells free DOX was also found in the cytoplasm. Cytotoxicity of the drug was concentration and exposure time dependent. In addition, PolyDOX significantly enhanced reactive oxygen species (ROS) level in both cells. PolyDOX also suppressed growth of breast tumor on female Sprague-Dawley (SD) rats as compared to phosphate buffer saline pH 7.4 (PBS) control group. In addition reduced level of serum enzymes (LDH and CPK) by PolyDOX formulation indicated less cardiotoxicity of DOX after loading in polymersomes. Results suggest that intracellular delivery of PolyDOX was depended on the CD44 expression level in cells due to, presence of hyaluronic acid on the surface of polymersomes, and could be used as a self-targeting drug delivery cargo in over-expressed CD44 glycoprotein cells of breast cancer.< Réduire
Mots clés en anglais
Polymersomes
Hyaluronan
Doxorubicin
Cell uptake
Cytotoxicity
Self-assembly
Origine
Importé de halUnités de recherche